Desmosine is a stable breakdown product of elastin that can be reliably measured in urine samples. We tested the hypothesis that higher baseline urine desmosine would be associated with higher mortality in 579 of 861 patients included in the recent ARDS Network trial of lower tidal volume ventilation (1). We also correlated urine desmosine levels with indices of disease severity. Finally, we assessed whether urine desmosine was lower in patients who received lower tidal volumes. Desmosine was measured by radioimmunoassay in urine samples from day 0, 1 and 3 of the study. The data were expressed as a ratio of urine desmosine to urine creatinine to control for renal dilution. The results show that higher baseline (day 0) urine desmosine to creatinine concentration was associated with a higher risk of death on adjusted analysis (OR 1.36, 95% confidence interval 1.02 to 1.82, p = 0.03). Urine desmosine increased in both ventilator groups from day 0 to day 3 but the average rise was higher in the 12 mL/kg predicted body weight group compared with the 6 ml/kg predicted body weight group (p = 0.053, repeated measures model). In conclusion, patients with acute lung injury ventilated with lower tidal volumes have lower urine desmosine levels, a finding that may reflect reduced extracellular matrix breakdown. These results illustrate the value of evaluating urinary biologic markers that may have prognostic and pathogenetic significance in acute lung injury.